Optically-controlled CNS dysfunction

Abstract

Provided herein are animals expressing light-responsive opsin proteins in the basal lateral amygdala of the brain and methods for producing the same wherein illumination of the light-responsive opsin proteins causes anxiety in the animal. Also provided herein are methods for alleviating and inducing anxiety in an animal as well as methods for screening for a compound that alleviates anxiety in an animal.

What is claimed is: 
     
       1. A system comprising:
 a) a non-human animal comprising a light-responsive opsin expressed in glutamatergic pyramidal neurons of the basolateral amygdala (BLA), wherein the opsin is an opsin which induces hyperpolarization of a neuron in response to light, and wherein the selective illumination of the opsin in the BLA-CeL induces anxiety of the animal; 
 b) a beveled guide cannula configured to be placed over the CeL to prevent light delivery to the BLA and to allow selective illumination of the CeA; and 
 c) a light source. 
 
     
     
       2. The system of  claim 1 , comprising a device configured to take electrophysiological recordings. 
     
     
       3. The system of  claim 1 , wherein the light source comprises an optical fiber. 
     
     
       4. The system of  claim 1 , further including a means for delivering one or more of a pharmacological agent, an electrical stimulus, or a magnetic stimulus to the non-human animal. 
     
     
       5. The system of  claim 1 , wherein the opsin comprises an amino acid sequence having at least 90% amino acid sequence identity to one of SEQ ID NOs:1-4. 
     
     
       6. The system of  claim 1 , wherein the opsin comprises an amino acid sequence having at least 95% amino acid sequence identity to one of SEQ ID NOs:1-4. 
     
     
       7. The system of  claim 1 , wherein the opsin comprises an endoplasmic reticulum (ER) export signal. 
     
     
       8. The system of  claim 7 , wherein the ER export signal comprises the amino acid sequence FXYENE (SEQ ID NO:12). 
     
     
       9. The system of  claim 1 , wherein the opsin comprises a membrane trafficking signal. 
     
     
       10. The system of  claim 9 , wherein the membrane trafficking signal comprises the amino acid sequence KSRITSEGEYIPLDQIDINV (SEQ ID NO:14). 
     
     
       11. The system of  claim 1 , wherein the opsin comprises an ER export signal and a membrane trafficking signal. 
     
     
       12. The system of  claim 1 , wherein the opsin is encoded by a nucleotide sequence that is operably linked to a CaMKIIα promoter.